Perceptions of weather-based pain forecasts and their effect on daily activities.

As studies begin to have more success uncovering the relationships between atmospheric conditions and pain, weather-based pain forecasting becomes more of a reality. In this study, a survey was used to determine if people living with migraines and/or other pain-related conditions are receptive to weather-based pain forecasts. Moreover, we wished to identify whether these forecasts actually impact the decision-making of those who use them. Survey respondents were generally eager to use these novel forecasts. Furthermore, when provided with different scenarios involving weather-based pain forecasts, the respondents' actions were altered. When a hypothetical forecast indicated that the weather was conducive to migraines or other types of pain, many indicated that they would likely take preventative measures (e.g., medication). Additionally, respondents were less likely to continue with a planned activity, regardless of length, as forecast severity increased. The results from this survey highlight the importance of developing and improving weather-based pain forecasting.

Longitudinal disparities in social determinants of health and COVID-19 incidence and mortality in the United States from the three largest waves of the pandemic.

The United States experienced at least five COVID-19 waves linked with different mutated SARS-CoV-2 variants including Alpha, Delta and Omicron. In addition to the variants, the intensity, geographical distribution, and risk factors related to those waves also vary within socio-demographic characteristics and timeframes. In this project, we have examined the spatial and temporal pattern of COVID-19 in the USA and its associations with Social Determinants of Health (SDoH) by utilizing the County Health Rankings & Roadmaps (CHRR) dataset. Our epidemiologic investigation at the county level showed that the burden of COVID-19 cases and deaths is higher in counties with high percentages of smoking, number of preventable hospital stays, primary care physician rate, the average daily density of PM2.5 and percentages of high proportions of Hispanic residents. In addition, the analysis also demonstrated that COVID-19 incidence and mortality had distinct characteristics in their association with SDoH variables. For example, the percentages of the population 65 and older had negative associations with incidence while a significant positive association with mortality. In addition to the elderly population, median household income, unemployment, and number of drug overdose deaths showed a mixed association with COVID-19 incidence and mortality. Our findings validate several influential factors found in the existing social epidemiology literature and highlight temporal associations between SDoH variables and COVID-19 incidence and mortality not yet frequently studied.

What to do about hepatocellular carcinoma: Recommendations for health authorities from the International Liver Cancer Association.

Hepatocellular carcinoma (HCC) is a major public health problem worldwide for which the incidence and mortality are similar, pointing to the lack of effective treatment options. Knowing the different issues involved in the management of HCC, from risk factors to screening and management, is essential to improve the prognosis and quality of life of affected individuals. This document summarises the current state of knowledge and the unmet needs for all the different stakeholders in the care of liver cancer, meaning patients, relatives, physicians, regulatory agencies and health authorities so that optimal care can be delivered to patients. The document was commissioned by the International Liver Cancer Association and was reviewed by senior members, including two ex-presidents of the Association. This document lays out the recommended approaches to the societal management of HCC based on the economic status of a given region.

A multi-analyte cell-free DNA-based blood test for early detection of hepatocellular carcinoma.

The limited performance of guideline-recommended abdominal ultrasound and serum alpha-fetoprotein (AFP) highlights the urgent, unmet need for new biomarkers for more accurate detection of early hepatocellular carcinoma (HCC). To this end, we have conducted a prospective clinical validation study to evaluate the performance of the HelioLiver Test, a multi-analyte blood test combining cell-free DNA methylation patterns, clinical variables, and protein tumor markers. A blinded, multicenter validation study was performed with 247 subjects, including 122 subjects with HCC and 125 control subjects with chronic liver disease. The performance of the HelioLiver Test was compared with AFP and the GALAD score as established HCC surveillance blood tests. The performance of the HelioLiver Test (area under the receiver operating characteristic curve [AUROC] = 0.944) was superior to both AFP (AUROC = 0.851; p < 0.0001) and GALAD (AUROC = 0.899; p < 0.0001). Using a prespecified diagnostic algorithm, the HelioLiver Test showed sensitivities of 85% (95% confidence interval [CI], 78%-90%) for HCC of any stage and 76% (95% CI, 60%-87%) for early stage (American Joint Committee on Cancer [AJCC] I and II) HCC. In contrast, AFP (≥20 ng/mL) alone and the GALAD score (≥-0.63) showed lower sensitivities of 62% (95% CI, 54%-70%) and 75% (95% CI, 67%-82%) for HCC overall, and 57% (95% CI, 40%-71%) and 65% (95% CI, 49%-79%) for early stage (AJCC I and II) HCC, respectively. The specificities of the HelioLiver Test (91%; 95% CI, 85%-95%), AFP (97%; 95% CI, 92%-99%), and the GALAD score (94%; 95% CI, 88%-97%) were similar for control subjects. The HelioLiver Test showed superior performance for HCC detection compared to with both AFP and the GALAD score and warrants further evaluation in HCC surveillance settings.

Geographical variability in the relationship between synoptic weather type and emergency department visits for pain across North Carolina.

Bodily pain plagues populations across the globe. Past studies have discovered some links between synoptic weather types and different kinds of pain. These relationships are essential as they can aide in treatment and potentially prevention of pain. In this study, the role of geographical characteristics on the relationships between synoptic weather type and pain were looked at. North Carolina was separated into three geographic sections: Appalachian Mountains, Piedmont Plateau, and Coastal Plain. Over a 7-year period, synoptic weather types and emergency department (ED) visits for various kinds of pain (migraine, fibromyalgia, rheumatoid arthritis, osteoarthritis, and general back pain) were collected. Bootstrapped confidence intervals of the mean number of population-adjusted ED visit rates (per 100,000 persons), for the different synoptic weather types, were compared across the different geographic regions. In the plateau region, Moist Tropical and Moist Moderate weather types were often linked to the highest rates of ED visits, while Polar weather types were frequently associated with the fewest visits. The mountainous portion of the state displayed similar patterns between synoptic weather types and the different forms of pain, with migraine and fibromyalgia being the exceptions. Few statistically significant relationships were noted for the coastal region.

The viral hepatitis B care cascade: A population-based comparison of immigrant groups.

BACKGROUND AND AIMS: The global burden of viral hepatitis B is substantial, and monitoring infections across the care cascade is important for elimination efforts. There is little information on care disparities by immigration status, and we aimed to quantify disease burden among immigrant subgroups. APPROACH AND RESULTS: In this population-based, retrospective cohort study, we used linked laboratory and health administrative records to describe the HBV care cascade in five distinct stages: (1) lifetime prevalence; (2) diagnosis; (3) engagement with care; (4) treatment initiation; and (5) treatment continuation. Infections were identified based on at least one reactive antigen or nucleic acid test, and lifetime prevalence was estimated as the sum of diagnosed and estimated undiagnosed cases. Care cascades were compared between long-term residents and immigrant groups, including subgroups born in hepatitis B endemic countries. Stratified analyses and multivariable Poisson regression were used to identify drivers for cascade progression. Between January 1997 and December 2014, 2,014,470 persons were included, 50,475 with infections, of whom 30,118 were engaged with care, 11,450 initiated treatment, and 6554 continued treatment >1 year. Lifetime prevalence was estimated as 163,309 (1.34%) overall, 115,722 (3.42%) among all immigrants, and 50,876 (9.37%) among those from highly endemic countries. Compared to long-term residents, immigrants were more likely to be diagnosed (adjusted rate ratio [aRR], 4.55; 95% CI, 4.46, 4.63), engaged with care (aRR, 1.07; 95% CI, 1.04, 1.09), and initiate treatment (aRR, 1.09; 95% CI, 1.03, 1.16). CONCLUSIONS: In conclusion, immigrants fared well compared to long-term residents along the care cascade, having higher rates of diagnosis and slightly better measures in subsequent cascade stages, although intensified screening efforts and better strategies to facilitate linkage to care are still needed.

Assessing Toxicity in Drug Trials in Liver Disease.

Since the early trials in viral hepatitis, more and more new drugs are being tested for use in various liver diseases. Since drug hepatotoxicity is a major cause of drugs under investigation not making it to market, the assessment of drug-induced liver injury in clinical trials of new drugs is crucial. This review will focus on the systems that are used to assess drug-induced liver injury in clinical trials and will discuss how some of these criteria are inappropriate or inaccurate in this function together with suggestions for improvement.

Viral hepatitis C cascade of care: A population-level comparison of immigrant and long-term residents.

BACKGROUND & AIMS: Viral hepatitis C represents a major global burden, particularly among immigrant-receiving countries such as Canada, where knowledge of disparities in hepatitis C virus among immigrant groups for micro-elimination efforts is lacking. We quantify the hepatitis C cascades of care among immigrants and long-term residents prior to the introduction of direct-acting antiviral medications. METHODS: Using laboratory and health administrative records, we described the hepatitis C virus cascades of care in terms of diagnosis, engagement with care, treatment initiation, and clearance in Ontario, Canada (1997-2014). We stratified the cascade by immigrant and long-term resident groups and identify drivers at each stage using multivariable Poisson regression. RESULTS: We included 940 245 individuals in the study with an estimated hepatitis C prevalence of 167 923 (1.4%) overall, 23 759 (0.7%) among all immigrants, and 6019 (1.1%) among immigrants from hepatitis C endemic countries. Overall there were 104 616 individuals with reactive antibody results, 73 861 tested for viral RNA, 52 388 with viral RNA detected, 50 805 genotyped, 13 159 on treatment and 3919 with evidence of viral clearance. Compared to long-term residents, immigrants showed increased nucleic-acid testing (aRR: 1.09 [95%CI: 1.08, 1.10]), treatment initiation (aRR: 1.46 [95%CI: 1.38, 1.54]), and higher clearance rates (aRR: 1.07 [95%CI: 1.03, 1.11]). CONCLUSIONS: Hepatitis C virus is more prevalent among long-term residents compared to immigrants overall, however, immigrants from endemic countries are an important subgroup to consider for future screening and linkage to care initiatives. These findings are prior to the introduction of newer medications and provide a population-based benchmark for follow-up studies and evaluation of treatment programs and surveillance activities.

Theoretical Matters: On the Need for Hazard and Disaster Theory Developed Through Interdisciplinary Research and Collaboration.

Hazard and disaster research requires a willingness to step outside of traditional disciplinary ontological and epistemological assumptions to both accommodate and integrate different perspectives. Moreover, the complex qualities of hazards and disasters necessitate interdisciplinary approaches to inform theory development that encompasses environmental, human, and infrastructure systems at multiple scales and units of analysis. Unfortunately, truly integrative hazard and disaster theory at a scale broad enough to account for the many systems and processes involved is currently limited. In this article, we argue that robust hazard and disaster theory can only arise from interdisciplinary research and collaboration. We examine challenges to the development of interdisciplinary hazard and disaster theory, and discuss the characteristics of theory necessary for the goal-oriented nature of research aimed at reducing disaster impact.

Interdisciplinary Research as an Iterative Process to Build Disaster Systems Knowledge.

Disasters occur at the intersections of social, natural, and built environments, and robust understanding of these interactions can only occur through insight generated from different disciplines. Yet, there are cultural, epistemological, and methodological differences across the many disciplines concerned with hazards and disasters that can make conducting interdisciplinary research difficult. Approaches are needed to overcome these challenges. This article argues that interdisciplinary disaster research can be successful when it entails an iterative process in which researchers from different disciplines work collaboratively and exert reciprocal influence to generate disaster systems knowledge. Disaster systems knowledge is interdisciplinary and is defined as a comprehensive understanding of the intersections of built, natural, and human environmental factors and their interplay in hazards and disasters. The iterative process can reduce disciplinary biases and privileges by encouraging collaboration among researchers to help ensure disciplinary knowledge complements other disciplinary knowledge, to ultimately generate interdisciplinary disaster systems knowledge. The article concludes by illustrating the process by analyzing a research case study of an interdisciplinary approach to volcanic risk reduction.

Relationship between synoptic weather type and emergency department visits for different types of pain across the Triangle region of North Carolina.

Many people around the world are impacted by some form of bodily pain. Outside factors, such as weather, are thought to help trigger pain, especially in those who have pain-related conditions. When it comes to human health and comfort, understanding the potential external factors that aide in triggering pain is essential. Identifying such factors makes prevention and treatment of pain more feasible. This study focused on how those who suffer from various pain-related conditions (fibromyalgia, rheumatoid arthritis, osteoarthritis, and general back pain) are impacted by different synoptic weather types (i.e., air masses). Synoptic weather types and emergency department (ED) visits for pain in select central North Carolina counties were collected over a seven-year period to determine a potential relationship. Bootstrapped confidence intervals revealed that moist tropical weather types resulted in the highest number of ED visits for each of the conditions examined, while moist polar weather types often resulted in the fewest. The barometric pressure changes associated with transitional weather types, which are often associated with fronts, did not have any significant relationships with pain.

Biology and significance of alpha-fetoprotein in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths globally due, in part, to the majority of patients being diagnosed with intermediate or advanced stage disease. Our increased understanding of the heterogeneous molecular pathogenesis of HCC has led to significant developments in novel targeted therapies. Despite these advances, there remains a high unmet need for new treatment options. HCC is a complex disease with multiple pathogenic mechanisms caused by a variety of risk factors, making it difficult to characterize with a single biomarker. In fact, numerous biomarkers have been studied in HCC, but alpha-fetoprotein (AFP) remains the most widely used and accepted serum marker since its discovery over 60 years ago. This review summarizes the most relevant studies associated with the regulation of AFP at the gene and protein levels; the pathophysiology of AFP as a pro-proliferative protein; and the correlation of AFP with molecular HCC subclasses, the vascular endothelial growth factor pathway and angiogenesis. Also described are the historical and current uses of AFP for screening and surveillance, diagnosis, its utility as a prognostic and predictive biomarker and its role as a tumour antigen in HCC. Taken together, these data demonstrate the relevance of AFP for patients with HCC and identify several remaining questions that will benefit from future research.

Design and Endpoints of Clinical Trials, Current and Future.

With the advent of several new systemic agents for the treatment of hepatocellular carcinoma and the prospect of more to come it is expected that many more clinical trials will be undertaken to establish the best treatment paradigm(s). In order to help develop the most efficient and most relevant clinical trials this review concentrates on endpoints that have been used in the past. Survival is the gold standard. None of the surrogate endpoints correspond completely with survival. In addition, alternative clinical trial designs are presented that may be more efficient than the usual phase I, II, and III clinical trial strategy that has been used in the past.

Outcomes of radiofrequency ablation as first-line therapy for hepatocellular carcinoma less than 3 cm in potentially transplantable patients.

BACKGROUND & AIMS: Radiofrequency ablation (RFA) is an effective treatment for single hepatocellular carcinoma (HCC) ≤3 cm. Disease recurrence is common, and in some patients will occur outside transplant criteria. We aimed to assess the incidence and risk factors for recurrence beyond Milan criteria in potentially transplantable patients treated with RFA as first-line therapy. METHODS: We performed a retrospective cohort study of potentially transplantable patients with new diagnoses of unifocal HCC ≤3 cm that underwent RFA as first-line therapy between 2000-2015. We defined potentially transplantable patients as those aged <70 years without any comorbidities that would preclude transplant surgery. Incidence of recurrence beyond Milan criteria was compared across 2 groups according to HCC diameter at the time of ablation: (HCC ≤2 cm vs. HCC >2 cm). Competing risks Cox regression was used to identify predictors of recurrence beyond Milan criteria. RESULTS: We included 301 patients (167 HCC ≤2 cm and 134 HCC >2 cm). Recurrence beyond Milan criteria occurred in 36 (21.6%) and 47 (35.1%) patients in the HCC ≤2 cm and the HCC >2 cm groups, respectively (p = 0.01). The 1-, 3- and 5-year actuarial survival rates after RFA were 98.2%, 86.2% and 79.0% in the HCC ≤2 cm group vs. 93.3%, 77.6% and 70.9% in the HCC >2 cm group (p = 0.01). Tumor size >2 cm (hazard ratio 1.94; 95%CI 1.25-3.02) and alpha-fetoprotein levels at the time of ablation (100-1,000 ng/ml: hazard ratio 2.05; 95%CI 1.10-3.83) were found to be predictors of post-RFA recurrence outside Milan criteria. CONCLUSION: RFA for single HCC ≤3 cm provides excellent short- to medium-term survival. However, we identified patients at higher risk of recurrence beyond Milan criteria. For these patients, liver transplantation should be considered immediately after the first HCC recurrence following RFA. LAY SUMMARY: Radiofrequency ablation and liver transplantation are treatment options for early stages of hepatocellular carcinoma (HCC). After ablation some patients will experience recurrence or metastatic spread of the initial tumor or may develop new tumors within the liver. Despite close follow-up, these recurrences can progress rapidly and exceed transplant criteria, preventing the patient from receiving a transplant. We identified that patients with HCC >2 cm and higher serum alpha-fetoprotein are at greater risk of recurrence beyond the transplant criteria. These data suggest that liver transplantation should be considered immediately after the first HCC recurrence for these patients.

Real-world health care utilization in treatment of HCV: Results from the Canadian SIMPLE observational trial.

Background: As hepatitis C virus (HCV) treatment continues to evolve, there is an ongoing need to understand and optimize real-world disease management. The primary objective of the SIMPLE study was to describe the real-life management of genotype 1 (G1) HCV in Canada treated with boceprevir + pegylated interferon and ribavirin therapy. Methods: This was an observational, prospective cohort, multicentre, non-interventional study of patients with G1 HCV. A single cohort of adult patients were to be managed as per standard of care (SoC) and treated with 4 weeks of PegRBV dual therapy, followed by boceprevir + PegRBV for 24-44 weeks, with 24-weeks follow-up. Treatment compliance, health care resource utilization (HCRU), HCV viral load, and hematological adverse event (AE) data were collected. Results: This study enrolled 159 patients. All investigators were well educated on the Canadian consensus guidelines for HCV management but only a minority of patients were treated according to treatment guidelines. Viral response was achieved by >50% of patients by week 8 of therapy and in 50%-60% of tested patients during follow-up. An average of 17.9 HCRU visits were reported during the study period. The most commonly used resources were nursing visits for routine follow-up. Conclusions: Results from this real-world study suggest that most patients were not treated according to the product monograph. Further studies are required to determine how oral treatments fit into this paradigm and how these findings extrapolate to the current treatment model. This study can serve as a benchmark for future real-world treatment including heath care utilization analyses.